RNAi Screen and Proteomics Reveal NXF1 as a Novel Regulator of IRF5 Signaling

Abstract Interferon regulatory factor 5 (IRF5) is a key transcription factor of innate immunity, which plays an important role in host restriction to viral infection and inflammation. Genome-wide association studies have implied the association of IRF5 with several autoimmune diseases, including sys...

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Autores principales:	Bishi Fu, Mengmeng Zhao, Lingyan Wang, Girish Patil, Jennifer A. Smith, Ignacio J. Juncadella, Ljiljana Zuvela-Jelaska, Martin E. Dorf, Shitao Li
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3b52515862064e31851be11761ce05b9
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spelling	oai:doaj.org-article:3b52515862064e31851be11761ce05b92021-12-02T15:06:12ZRNAi Screen and Proteomics Reveal NXF1 as a Novel Regulator of IRF5 Signaling10.1038/s41598-017-02857-z2045-2322https://doaj.org/article/3b52515862064e31851be11761ce05b92017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02857-zhttps://doaj.org/toc/2045-2322Abstract Interferon regulatory factor 5 (IRF5) is a key transcription factor of innate immunity, which plays an important role in host restriction to viral infection and inflammation. Genome-wide association studies have implied the association of IRF5 with several autoimmune diseases, including systemic lupus erythematosus (SLE), Sjogren’s syndrome, inflammatory bowel disease and multiple sclerosis. However, the regulation of IRF5-mediated immunity is not well understood. To uncover new regulators in IRF5 pathway, we used two “omics” approaches: affinity purification coupled with mass spectrometry and a high throughput RNAi screen. Proteomics identified 16 new IRF5 interactors while RNAi-mediated knockdown found 43 regulators of the TLR7-dependent IRF5 signaling pathway. NXF1 was identified in both screens. Stimulation with TLR7 ligand enhances formation of IRF5-NXF1 protein complexes. Gain or loss-of-function experiments revealed NXF1 selectively regulates TLR7-driven IRF5 transcriptional activity, suggesting a new role for NXF1 in the IRF5 signaling pathway.Bishi FuMengmeng ZhaoLingyan WangGirish PatilJennifer A. SmithIgnacio J. JuncadellaLjiljana Zuvela-JelaskaMartin E. DorfShitao LiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bishi Fu Mengmeng Zhao Lingyan Wang Girish Patil Jennifer A. Smith Ignacio J. Juncadella Ljiljana Zuvela-Jelaska Martin E. Dorf Shitao Li RNAi Screen and Proteomics Reveal NXF1 as a Novel Regulator of IRF5 Signaling
description	Abstract Interferon regulatory factor 5 (IRF5) is a key transcription factor of innate immunity, which plays an important role in host restriction to viral infection and inflammation. Genome-wide association studies have implied the association of IRF5 with several autoimmune diseases, including systemic lupus erythematosus (SLE), Sjogren’s syndrome, inflammatory bowel disease and multiple sclerosis. However, the regulation of IRF5-mediated immunity is not well understood. To uncover new regulators in IRF5 pathway, we used two “omics” approaches: affinity purification coupled with mass spectrometry and a high throughput RNAi screen. Proteomics identified 16 new IRF5 interactors while RNAi-mediated knockdown found 43 regulators of the TLR7-dependent IRF5 signaling pathway. NXF1 was identified in both screens. Stimulation with TLR7 ligand enhances formation of IRF5-NXF1 protein complexes. Gain or loss-of-function experiments revealed NXF1 selectively regulates TLR7-driven IRF5 transcriptional activity, suggesting a new role for NXF1 in the IRF5 signaling pathway.
format	article
author	Bishi Fu Mengmeng Zhao Lingyan Wang Girish Patil Jennifer A. Smith Ignacio J. Juncadella Ljiljana Zuvela-Jelaska Martin E. Dorf Shitao Li
author_facet	Bishi Fu Mengmeng Zhao Lingyan Wang Girish Patil Jennifer A. Smith Ignacio J. Juncadella Ljiljana Zuvela-Jelaska Martin E. Dorf Shitao Li
author_sort	Bishi Fu
title	RNAi Screen and Proteomics Reveal NXF1 as a Novel Regulator of IRF5 Signaling
title_short	RNAi Screen and Proteomics Reveal NXF1 as a Novel Regulator of IRF5 Signaling
title_full	RNAi Screen and Proteomics Reveal NXF1 as a Novel Regulator of IRF5 Signaling
title_fullStr	RNAi Screen and Proteomics Reveal NXF1 as a Novel Regulator of IRF5 Signaling
title_full_unstemmed	RNAi Screen and Proteomics Reveal NXF1 as a Novel Regulator of IRF5 Signaling
title_sort	rnai screen and proteomics reveal nxf1 as a novel regulator of irf5 signaling
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3b52515862064e31851be11761ce05b9
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_version_	1718388575554240512

RNAi Screen and Proteomics Reveal NXF1 as a Novel Regulator of IRF5 Signaling

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